A large body of prior art exists which teaches methods and apparatus for carrying out the chemical analysis of biological fluids. Some of the prior art utilizes test packages which contain prepackaged reagents isolated from a sample chamber by seals. These packages are utilized in an environment wherein the steps of the process are carried out serially in time as each package is moved from one station to another in an enclosed chemical analysis system. Other prior art utilizes test packages without integral cuvettes in a similar serial chemical analysis system. Still other prior art utilizes spinning rotors which act in combination with test packages and utilizes centrifugal force to open reagent packages into a chamber which is a combined mixing chamber-cuvette. Still other rotary systems utilize disposable trays and carry out in situ chemical analysis. Exemplary prior art is as follows:
U.S. Pat. No. 3,532,470 shows a sample holder having a chamber adapted to hold a sample. The holder can be centrifuged to separate serum from blood. After separation, the sample is transferred to a mixing chamber where prepackaged reagents are introduced. This arrangement has no cuvette per se and analysis is not carried out in situ in a rotor arrangement. Thus, while the package structure is very similar to that of the present application, the combination of a test package with prepackaged reagents, a cuvette and a rotor are neither taught nor suggested.
U.S. Pat. No. 3,476,515 shows a flexible test package having an envelope-like configuration wherein selected pods containing reagent may be protected from breaking while other selected pods may have their seals broken by applying pressure to the remainder of the bag. Then, by the application and release of a force on the liquid, the reagents and sample are thoroughly mixed. The shape of the test pack of this patent is totally different and, on the shelf, contains no preformed cuvette chamber. In addition, the patent does not suggest that the test package disclosed can be used in a rotary environment.
U.S. Pat. No. 3,477,821 shows a package which includes an integral cuvette and prepackaged reagents. The package is not adapted for use with a rotor which, upon rotation, permits mixing of a sample and a reagent prior to it being introduced in to cuvette. In the reference, mixing is accomplished by a magnetic stirrer in the cuvette. There is no showing of the combination of a test package with prepackaged reagents and a rotor which carries out mixing and measuring in situ.
U.S. Pat. No. 3,497,320 shows a package wherein prepackaged reagents are disposed alongside a mixing chamber-cuvette. The test package of the reference, while accomplishing the same end result, does not use rotating means to carry out its method. The present invention can be distinguished over this reference on the basis that the combination of the particular test pack with a rotor has not been taught. U.S. Pat. No. 3,540,857 shows a sample holder which has a chamber to which pressure may be applied to force a sample through a filter to another chamber. This holder has no cuvette nor does it have prepackaged reagents.
U.S. Pat. No. 3,540,858 shows a sample holder which has a chamber to which pressure is applied to force a sample through a filter to another chamber. This holder has no cuvette as can be seen from the fact that for optical density testing, the sample with reagent is removed from the holder and pumped into the cell of an analyzer. The patent shows the sample holders arranged in a circle and disposed on a turntable.
U.S. Pat. No. 3,547,547 shows a type of loading disk which, while it has an integral cuvette, does not use prepackaged reagents.
U.S. Pat. No. 3,555,284 shows a transfer disk which does not include prepackaged reagents or an integral cuvette.
U.S. Pat. No. 3,582,218 shows a disposable plastic cuvette into which samples and reagents are transferred by centrifugal force. The samples and reagents are not prepackaged but are introduced sequentially into a holding chamber. All the samples and reagents are first transferred to a cuvette where mixing takes place.
U.S. Pat. No. 3,586,484 shows a transfer disk which does not have an integral cuvette or prepackaged reagents.
U.S. Pat. No. 3,759,666 shows a rotatable loading disk wherein the absorbances of a liquid sample and a reference sample are intercompared. The system includes a series of cuvettes arranged around the periphery of a rotor so that when it is spun, centrifugal force simultaneously mixes and transfers reagents and sample to the cuvettes where an analysis is made spectrophotometrically. The loading disk contains rows of cavities arranged concentrically. Samples to be analyzed are placed in the inner cavities and reagents are placed in cavities at greater radial distance than those containing the serum samples. The disk is then indexed and positioned in the rotor and, as the rotor is spun, centrifugal force moves the sample to the cavity containing the reagent, where they are mixed. The resulting mixture is then moved through a communicating passage to a cuvette where measurements are carried out. In this reference, there are no prepackaged reagents and the cuvettes are not integral with the specimen and the reagent package. The specimen and reagents must be introduced into the disk prior to loading. Also, since the cuvettes of the reference appear to be integral with the rotor, cleaning of the cuvettes is required after each measurement. This reference shows no prepackaged reagent test pack with integral cuvette.
U.S. Pat. No. 3,856,470 shows a transfer disk for individually storing the various constituents of one or more independent reactions and a cuvette rotor. This reference shows no prepackaged reagents and includes cuvettes which are not integral with the disk which holds the sample and reagents.
U.S. Pat. No. 4,135,883 shows a microprocessor controlled centrifuge having a group of cuvettes therein. The apparatus also includes a microdiluter. The cuvettes have hollow main bodies made of transparent material to allow analysis of the specimen therein by a spectrophotometer which reads the cuvettes while rotating. Bags of reagent are received within the cuvettes and are designed to burst under centrifugal force. This permits reagent to flow from the bags into a test chamber within the cuvette's main body.
This reference broadly shows all the elements of an analytical chemistry system. The combination of the present application differs from the reference in that the present test pack does not require centrifugal force to break reagent bags but uses mechanical pressure applied selectively to introduce a reagent and low speed rotation to accomplish mixing. Also, the test pack of the reference is rigid and must be loaded with burstable bags of reagent while the test pack of the present disclosure includes reagent portions, mixing chamber and cuvette in an integral package which is totally disposable. In addition, the combination of the present disclosure does not require high centrifugal speeds permitting a simple and less expensive mechanical arrangement.
From all the foregoing, it should be clear that though the cited prior art is very significant, none of the above cited references appreciate that the combination of the test package and rotor of the present invention could provide a compact, inexpensive way for carrying out in situ clinical analysis of biological fluids.
It is, therefore an object of the present invention to provide a chemical anaylsis system in which a test package and rotor combination permit in situ chemical analysis to be carried out.
Another object is to provide a test package having an integral sample chamber, integral, prepackaged reagent chambers and an integral cuvette.
Another object is to provide a test package which is completely disposable and inexpensive.
Still another object is to provide a rotational chemical analysis system which does not require high speed rotation.
Yet another object is to provide a chemical analysis system which is capable of providing batch testing at higher throughput rates than known prior art systems.